Hydrogen Sulfide Is a Novel Protector of the Retinal Glycocalyx and Endothelial Permeability Barrier.
Hydrogen Sulfide Is a Novel Protector of the Retinal Glycocalyx and Endothelial Permeability Barrier.
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DOI：
10.3389/fcell.2021.724905
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发表时间：
2021
影响因子：
5.5
通讯作者：
Whatmore JL
中科院分区：
文献类型：
--
作者：
Allen CL;Wolanska K;Malhi NK;Benest AV;Wood ME;Amoaku W;Torregrossa R;Whiteman M;Bates DO;Whatmore JL
在糖尿病患者中观察到抗炎气体递质硫化氢（H2S）的水平显著降低，并与微血管功能障碍相关。H2S可以通过防止内皮糖萼的损失来保护微血管。我们检验了H2S可以预防或治疗糖尿病视网膜微血管内皮功能障碍的假设。体外培养牛视网膜内皮细胞（BRECs），分别暴露于正常葡萄糖（NG，5.5mmol/L）和高糖（HG，25 mmol/L）±缓释H2S供体NaGYY 4137。测量糖萼覆盖率（用WGA-FITC染色）和钙黄绿素标记的单核细胞粘附。在体内，在正常和链脲佐菌素（STZ）诱导的糖尿病大鼠进行眼底荧光血管造影（FFA）。动物接受眼内注射NaGYY 4137（1 μM）或尿道靶向H2S供体AP 39（100 nM），同时使用STZ（预防）或在STZ（治疗）后第6天，并使用间质荧光与血管荧光的比值来估计表观渗透性。NaGYY 4137防止HG诱导的BREC糖萼损失，增加单核细胞与BREC的结合（p ≤ 0.001），并增加总糖萼覆盖率（p ≤ 0.001）。在大鼠中，通过用NaGYY 4137和AP 39预处理（p <0.05）显著防止STZ诱导的表观视网膜血管通透性的增加（p ≤ 0.01），并且通过STZ后施用使其稳定。NaGYY 4137还减少了两组中糖尿病视网膜中无细胞毛细血管（胶原IV + /IB 4-）的数量（p ≤ 0.05）。我们得出结论，NaGYY 4137和AP 39保护视网膜糖萼和内皮通透性屏障免受糖尿病相关的完整性丧失，并减少糖尿病视网膜病变（DR）的进展。因此，靶向糖萼的硫化氢供体可能是DR的治疗候选者。
Significantly reduced levels of the anti-inflammatory gaseous transmitter hydrogen sulfide (H2S) are observed in diabetic patients and correlate with microvascular dysfunction. H2S may protect the microvasculature by preventing loss of the endothelial glycocalyx. We tested the hypothesis that H2S could prevent or treat retinal microvascular endothelial dysfunction in diabetes. Bovine retinal endothelial cells (BRECs) were exposed to normal (NG, 5.5 mmol/L) or high glucose (HG, 25 mmol/L) ± the slow-release H2S donor NaGYY4137 in vitro. Glycocalyx coverage (stained with WGA-FITC) and calcein-labeled monocyte adherence were measured. In vivo, fundus fluorescein angiography (FFA) was performed in normal and streptozotocin-induced (STZ) diabetic rats. Animals received intraocular injection of NaGYY4137 (1 μM) or the mitochondrial-targeted H2S donor AP39 (100 nM) simultaneously with STZ (prevention) or on day 6 after STZ (treatment), and the ratio of interstitial to vascular fluorescence was used to estimate apparent permeability. NaGYY4137 prevented HG-induced loss of BREC glycocalyx, increased monocyte binding to BRECs (p ≤ 0.001), and increased overall glycocalyx coverage (p ≤ 0.001). In rats, the STZ-induced increase in apparent retinal vascular permeability (p ≤ 0.01) was significantly prevented by pre-treatment with NaGYY4137 and AP39 (p < 0.05) and stabilized by their post-STZ administration. NaGYY4137 also reduced the number of acellular capillaries (collagen IV + /IB4-) in the diabetic retina in both groups (p ≤ 0.05). We conclude that NaGYY4137 and AP39 protected the retinal glycocalyx and endothelial permeability barrier from diabetes-associated loss of integrity and reduced the progression of diabetic retinopathy (DR). Hydrogen sulfide donors that target the glycocalyx may therefore be a therapeutic candidate for DR.
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DOI：
10.1097/shk.0000000000000478
发表时间：
2016-01
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
Ahmad A;Olah G;Szczesny B;Wood ME;Whiteman M;Szabo C
通讯作者：
Szabo C
DOI：
10.1016/j.niox.2015.05.001
发表时间：
2015-09-15
期刊：
Nitric oxide : biology and chemistry
影响因子：
--
作者：
Ikeda K;Marutani E;Hirai S;Wood ME;Whiteman M;Ichinose F
通讯作者：
Ichinose F
影响因子：
7.3
作者：
Brancaleone, V.;Roviezzo, F.;Cirino, G.
通讯作者：
Cirino, G.
影响因子：
7.4
作者：
Carballal, Sebastian;Trujillo, Madia;Alvarez, Beatriz
通讯作者：
Alvarez, Beatriz
硫化氢在视网膜疾病中的作用
影响因子：
5.6
作者：
Du J;Jin H;Yang L
通讯作者：
Yang L